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目的:通过观察解虑安神汤乙酸乙酯提取部位(J-A)对焦虑症动物模型行为学及脑内γ-氨基丁酸受体A亚型(GABAA-R)正性变构剂3α,5α-四氢孕酮(allopregnanolone,ALLO)的影响,探讨其抗焦虑的作用机制。方法:雄性小鼠随机分成隔离组和群养组。群养组每笼10只群养,作为正常对照组;隔离组小鼠单笼单只隔离饲养,复制社会隔离焦虑模型,随机分为正常对照组[0.5%聚氧乙烯山梨糖醇酐单油酸酯(吐温-80)]、模型组(0.5%吐温-80)、地西泮组(0.002 g·kg-1)、解虑安神汤乙酸乙酯提取部位组(J-A,0.21 g·kg-1)。从造模第3周开始ig给药,造模4周,于末次给药后1 h用高架十字迷宫(EPM)进行行为学测定,记录小鼠在EPM开臂、闭臂停留时间,进入开臂、闭臂次数,计算开放臂进入次数比例(OE%)及开放臂停留时间比例(OT%);行为学实验结束后,测定脑内ALLO的含量。结果:与模型组相比,J-A组可缩短小鼠在闭臂停留时间(186.14±50.86)s,(245.47±35.00)s、增加进入开臂次数的百分比(19.38±15.57)%,(7.34±9.68)%,差异有显著性意义(P<0.05);并具有延长小鼠在开臂停留时间,增加小鼠进入开臂次数、减少进入闭臂次数的趋势。脑内ALLO水平测定表明,与模型组相比,J-A组可增加小鼠脑内ALLO的水平,A依次为(0.90±0.13),(0.77±0.11),差异有显著性意义(P<0.05)。结论:解虑安神汤乙酸乙酯提取部位可能通过增加脑内ALLO的水平从而增强GABAA-R的功能发挥抗焦虑作用。
OBJECTIVE: To observe the behavioral changes of behavior model of anxiety animal and the effects of GABAA-R positive allosteric agents 3α, 5α- The effects of allopregnanolone (ALLO) on the anti-anxiety mechanism were explored. Methods: Male mice were randomly divided into isolation group and group raising group. Groups of 10 mice per cage were housed as normal control group. Isolated mice were isolated and housed individually and were divided into normal control group [0.5% polyoxyethylene sorbitan mono-oil (Tween-80), model group (0.5% Tween-80) and diazepam group (0.002 g · kg -1) kg-1). From the third week of modeling, ig administration was started and the model was established for 4 weeks. Behavioral tests were performed at 1 h after the last administration with an elevated positive maze (EPM) The number of arms and arms closed, the ratio of open arms (OE%) and the percentage of open arms (OT%) were calculated. After the behavioral experiments, the contents of ALLO in brain were measured. Results: Compared with the model group, the JA group can shorten the retention time (186.14 ± 50.86) s, (245.47 ± 35.00) s, increase the percentage of open arms (19.38 ± 15.57)%, (7.34 ± 9.68)% respectively. The difference was significant (P <0.05). It also had the effect of prolonging the residence time of the mice in the open arms, increasing the number of mice entering the open arms and decreasing the number of entering the closed arms. The levels of ALLO in brain showed that compared with model group, JA group increased the levels of ALLO in brain of mice (A (0.90 ± 0.13) and (0.77 ± 0.11), respectively, with significant difference (P <0.05) . Conclusion: It is possible that Anxiety Decoction Ethyl Acetate Extract may play an anxiolytic role by enhancing the level of ALLO in the brain and enhancing the function of GABAA-R.